C-reactive protein in outpatients with acute exacerbation of COPD: its relationship with microbial etiology and severity

Miguel Gallego,1–3 Xavier Pomares,1,3 Silvia Capilla,4 Maria Angeles Marcos,5,6 David Suárez,7 Eduard Monsó,1–3,* Concepción Montón1,8,* 1Department of Respiratory Medicine, Hospital de Sabadell, Institut Universitari Parc Taulí-UAB, Sabadell, 2Universitat Autònoma de Barcelona, Esfera UAB, Barcelona, 3CIBER de Enfermedades Respiratorias, CIBERES, Bunyola, 4Laboratory of Microbiology, Institut Universitari Parc Taulí-UAB, Sabadell, 5Department of Clinical Microbiology, Hospital Clínic, 6ISGlobal, Barcelona Centre for International Health Research (CRESIB), Hospital Clínic, Universitat de Barcelona, Barcelona, 7Epidemiology and Assessment Unit, Fundació Parc Taulí, Universitat Autònoma de Barcelona, Sabadell, 8Health Services Research on Chronic Diseases Network-REDISSEC, Galdakao, Spain *These authors contributed equally to this work Background: C-reactive protein (CRP) measurement has proven valuable for detecting exacerbations, but its usefulness in predicting etiology remains controversial. Likewise, its potential value as a marker of severity, which is well established in patients with pneumonia, remains unproven in chronic obstructive pulmonary disease (COPD) exacerbations. Methods: A cohort study of 118 patients with severe COPD and acute infectious exacerbations were included and followed up over 1 year. Episodes of exacerbations meeting Anthonisen’s criteria type I–II were evaluated, analyzing the etiology and inflammatory response as measured by CRP in blood. Results: A total of 380 episodes were recorded. Full microbiological analysis was available in 265 samples. Haemophilus influenzae was the most commonly isolated bacteria and rhinovirus the most common virus. Median CRP levels from the 265 episodes were higher in the cases with positive cultures for bacteria (58.30 mg/L, interquartile range [IQR] 21.0–28.2) than in episodes only positive for viruses (37.3 mg/L, IQR 18.6–79.1) and cases negative for any microorganism (36.4 mg/L, IQR 10.8–93.7) (P<0.014). H. influenzae and Streptococcus pneumoniae reached the highest CRP levels of 74.5 mg/L (IQR 23.9–167.9) and 74.1 mg/L (IQR 42.0–220.7), respectively. In the 380 exacerbations studied, 227 (~60%) were community-managed, while 153 (~40%) required hospital admission. In the multivariate analysis to assess the influence of inflammatory response on exacerbation severity, baseline hypercapnia (odds ratio [OR]: 2.70, 95% confidence interval [CI]: 1.46–4.9) and CRP levels >100 mg/L (OR: 4.23, 95% CI: 2.12–8.44) were independent predictors after adjustment for baseline characteristics. Conclusion: CRP level was higher in bacterial infections, especially when H. influenzae and S. pneumoniae were isolated. CRP values >100 mg/L were associated with a fourfold increased risk of hospital admission. Therefore, CRP blood levels may be a useful biomarker in the management of exacerbations appearing in patients with severe disease. Keywords: COPD exacerbations, C-reactive protein, viruses, hospital admissio